Stanley Jone A, Sivakumar Kirthiram K, Arosh Joe A, Burghardt Robert C, Banu Sakhila K
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas.
Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
Biol Reprod. 2014 Jul;91(1):12. doi: 10.1095/biolreprod.113.113332. Epub 2014 May 7.
Environmental contamination of drinking water with chromium (Cr) has been increasing in more than 30 cities in the United States. Previous studies from our group have shown that Cr affects reproductive functions in female Sprague Dawley rats. Although it is impossible to completely remove Cr from the drinking water, it is imperative to develop effective intervention strategies to inhibit Cr-induced deleterious health effects. Edaravone (EDA), a potential inhibitor of free radicals, has been clinically used to treat cancer and cardiac ischemia. This study evaluated the efficacy of EDA against Cr-induced ovarian toxicity. Results showed that maternal exposure to CrVI in rats increased follicular atresia, decreased steroidogenesis, and delayed puberty in F1 offspring. CrVI increased oxidative stress and decreased antioxidant (AOX) enzyme levels in the ovary. CrVI increased follicle atresia by increased expression of cleaved caspase 3, and decreased expression of Bcl2 and Bcl2l1 in the ovary. EDA mitigated or inhibited the effects of CrVI on follicle atresia, pubertal onset, steroid hormone levels, and AOX enzyme activity, as well as the expression of Bcl2 and Bcl2l1 in the ovary. In a second study, CrVI treatment was withdrawn, and F1 rats were injected with estradiol (E₂) (10 μg in PBS/ethanol per 100 g body weight) for a period of 2 wk to evaluate whether E₂ treatment will restore Cr-induced depletion of AOX enzymes. E₂ restored CrVI-induced depletion of glutathione peroxidase 1, catalase, thioredoxin 2, and peroxiredoxin 3 in the ovary. This is the first study to demonstrate the protective effects of EDA against any toxicant in the ovary.
美国30多个城市饮用水中铬（Cr）的环境污染一直在增加。我们团队之前的研究表明，铬会影响雌性斯普拉格-道利大鼠的生殖功能。尽管不可能完全去除饮用水中的铬，但开发有效的干预策略以抑制铬对健康的有害影响势在必行。依达拉奉（EDA）是一种潜在的自由基抑制剂，已在临床上用于治疗癌症和心脏缺血。本研究评估了依达拉奉对铬诱导的卵巢毒性的疗效。结果表明，大鼠母体暴露于六价铬会增加卵泡闭锁，降低类固醇生成，并使F1代后代青春期延迟。六价铬增加了卵巢中的氧化应激并降低了抗氧化（AOX）酶水平。六价铬通过增加卵巢中裂解的半胱天冬酶3的表达以及降低Bcl2和Bcl2l1的表达来增加卵泡闭锁。依达拉奉减轻或抑制了六价铬对卵泡闭锁、青春期开始、类固醇激素水平和AOX酶活性的影响，以及卵巢中Bcl2和Bcl2l1的表达。在第二项研究中，停止六价铬处理，给F1代大鼠注射雌二醇（E₂）（每100克体重10μg溶于PBS/乙醇中），持续2周，以评估E₂处理是否能恢复铬诱导的AOX酶消耗。E₂恢复了六价铬诱导的卵巢中谷胱甘肽过氧化物酶1、过氧化氢酶、硫氧还蛋白2和过氧化物还原酶3的消耗。这是第一项证明依达拉奉对卵巢中任何毒物具有保护作用的研究。
